Abstract Childhood adversity accounts for 50-75% of the population attributable risk for alcoholism, drug abuse, depression, and suicide. Recent work has also documented enduring effects of childhood maltreatment on adult neurobiology, including alterations in cortical and limbic structures and reprogramming of HPA-axis mediated stress responses. Notably missing, however, is an understanding of how the potential neurobiological sequelae of chronic childhood adversity shape the vital adult activity of caring for an infant, and how this in turn affects early brain development. The proposed program of research seeks, for the first time, to link processes across neurobiological, neuroendocrine, and behavioral levels to examine how the impact of early adversity is conveyed from mother to child, among 150 mothers and their infants. To accomplish these aims the program is led by multiple principal investigators with specific expertise in: (1) mother-infant communication; (2) neurobiological effects of childhood abuse and (3) neonatal neuroimaging. The first aim of the study is to assess whether adversity- related alterations in structure, function or connectivity of maternal brain regions critical to stress regulation, including the amygdala, hippocampus/subiculum, and medial orbitofrontal cortex (MOFC), are associated with differences in maternal stress response during an in-scanner psychosocial stress challenge. The second aim is to assess whether childhood adversity is associated with differences in mother's interactions with their infants at 4 and 12 months of age. Finally, we will assess longitudinally the degree to which maternal disrupted communication leads to impairments in infant stress regulation, amygdala hypertrophy and altered functional connectivity at one year of age. A substudy will also evaluate the contribution of prenatal factors including acute and chronic stress hormone measures, maternal psychiatric symptomatology and partner conflict. Childhood adversity and disrupted parenting are the root preventable causes for a host of medical and psychiatric disorders including addiction that result in billions of dollars in health care expenditures. A detailed understanding of underlying mechanisms, critical time points, and mediating factors is necessary to design targeted interventions to preempt the adverse consequences of early adversity. The proposed program of research will provide data on potential early biomarkers for infant risk that are much more specific than broad maternal psychosocial factors and could lead to earlier and more effective identification of, and intervention in, risk-related developmental trajectories.